Transition-metal mediated exo selective and enantioselective Diels-Alder reactions for the preparation of octalones with unusual stereochemistries. Reactions of 2-cobaloxime substituted 1,3-dienes with cyclohexenone in optically active Lewis acid catalyzed [4 + 2] cycloadditions

Article abstract of DOI:10.1016/S0022-328X(98)01036-5

2-Cobaloxime-E-1,3-pentadienyl complexes (cobaloxime = pyridine(dimethyl or diphenylglyoxime)₂Cobalt (III)) react with cyclohexenone in enantioselective Lewis acid catalyzed [4 + 2] cycloaddition reactions. These cycloaddition reactions produce octalones with cis ring junctions through exo transition states. The octalones are removed from the cobalt via demetallation reactions which replace the cobalt with a hydrogen and provide pyr(dmg)₂CoMe which can be recycled into the synthesis of the starting dienyl complex. The enantiomeric purity of the demetallated octalones was determined by gas chromatographic analysis.

Full text of DOI:10.1016/S0022-328X(98)01036-5

Journal of Organometallic Chemistry 577 (1999) 120–125
Transition-metal mediated exo selective and enantioselective
Diels–Alder reactions for the preparation of octalones with unusual
stereochemistries. Reactions of 2-cobaloxime substituted 1,3-dienes
with cyclohexenone in optically active Lewis acid catalyzed [4+2]
cycloadditions
1
,2
B. Matthew Richardson, Cynthia S. Day , Mark E. Welker *
Department of Chemistry, Wake Forest Uni6ersity, PO Box 7486, Winston-Salem, NC 27109, USA
Received 11 August 1998
Abstract
-Cobaloxime-E-1,3-pentadienyl complexes (cobaloxime=pyridine(dimethyl or diphenylglyoxime) Cobalt (III)) react with
2
2
cyclohexenone in enantioselective Lewis acid catalyzed [4+2] cycloaddition reactions. These cycloaddition reactions produce
octalones with cis ring junctions through exo transition states. The octalones are removed from the cobalt via demetallation
reactions which replace the cobalt with a hydrogen and provide pyr(dmg) CoMe which can be recycled into the synthesis of the
2
starting dienyl complex. The enantiomeric purity of the demetallated octalones was determined by gas chromatographic analysis.
©
1999 Elsevier Science S.A. All rights reserved.
Keywords: Dienyl complexes; Diels–Alder reactions; Cycloaddition reactions; Lewis acid catalysis
1
. Introduction
major products. We have postulated that this anti (exo)
selectivity is a result of metal ligand set-dienophile
steric interactions which disfavor endo transition states.
Other groups [3], in particular Wulff [4a] and Barluenga
[4b], have also reported that the alternate strategy of
transition-metal substitution in the dienophiles can be
used to effect exo selective 4+2 cycloadditions.
Cyclohexenones (2) have traditionally been poor
dienophiles in thermal and Lewis acid catalyzed Diels–
Alder reactions [5]. Last year we reported that our very
reactive cobaloxime substituted dienes (1) would react
with these dienophiles under mild conditions to pro-
duce high yields of cycloadducts with excellent
diastereoselectivity and without concomitant ring junc-
tion isomerization from cis to trans octalones [1h].
Here, we report our results for enantioselective Lewis
acid catalyzed Diels–Alder reactions [6] of cobaloxime
dienyl complexes (1) with cyclohexenone (2).
Over the last several years, we have prepared cobalt
substituted 1,3-dienes (1) and examined the rates, re-
gioselectivities, and stereoselectivities of their reactions
with dienophiles in Diels–Alder reactions [1]. Tada and
co-workers have reported alternative preparations of
some cobaloxime substituted dienes as well as results of
their cycloaddition reactions [2]. The diastereoselectivi-
ties of the Diels–Alder reactions of these cobaloxime
dienyl complexes (1) are unusual for acyclic dienes in
that products arising from exo transition states are the
*
Corresponding author. Fax:
+1-336-758-4321; e-mail:
welker@wfu.edu
1
Author to whom inquiries concerning X-ray crystallography
should be addressed.
2
Henry Dreyfus Teacher-Scholar Awardee (1994–99).
0022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(98)01036-5

B.M. Richardson et al. / Journal of Organometallic Chemistry 577 (1999) 120–125
121
The (−)-bis-trifluromethylsulfonamidebromoborane (6)
reported by Corey [7] was prepared from the corre-
sponding diamine [8]. Matteson [9] and Brown [10]
have both reported the preparation of (+)-isopinocam-
pheylchloroborane (7). Hawkins [11] has shown that
(
1R, 2R)-napthylcyclohexylborondichloride (8b) is an
effective Diels–Alder catalyst. Nakai [12] and Reetz
13] reported the now heavily utilized (R)-1,1%-bi-2-
[
naptholtitanium dichloride catalyst (9). Boron dichlo-
ride (8b) was prepared from the (1R, 2R) methoxy
borinate ester (8a) and the structure of that compound
was confirmed by single crystal X-ray crystallography
2. Results and discussion
[14].
We have previously surveyed a variety of achiral
Lewis acid catalysts and developed a good, general
protocol for Lewis acid catalyzed Diels–Alder reactions
using the dienyl complexes (1) shown above [1d,h]. This
protocol calls for the initial treatment of dienyl com-
plexes (1) with two equivalents of AlMe , which results
3
in CH4 expulsion, and replacement of the bridging
glyoxime OHs with AlMe groups (5). This Lewis for
2
Bronsted acid exchange in the metal’s equatorial ligand
set results in increased steric bulk of the ligands and
enhanced exo diastereoselectivity of subsequent Diels–
Alder reactions [1d,h]. After this equatorial ligand mod-
ification, the Lewis acid catalyst to be used in the
Diels–Alder reaction and the dienophile were added.
We adopted this procedure in the present study of
optically active Lewis acid catalysts. The choice of
possible optically active Lewis acids to screen was
based on the reactivity of the achiral Lewis acids tested
earlier [1d,h]. Highest yields, diastereoselectivities, and
rates of reaction came from the use of the boron mono
and dihalide containing Lewis acids as well as titanium
dihalide Lewis acids so we picked four optically active
Lewis acids of these types to screen for enantioselectiv-
ity [1d,h]. We chose cyclohexenone (2) as a test
dienophile because of its extremely high anti (exo)
diastereoselectivity in achiral Lewis acid catalyzed reac-
tions of 1 [1d], the ease of demetallation of cycload-
ducts (3) to yield octalones (4), and the ease of
enantiomer separation of octalones (4) using a commer-
cially available Chiraldex G-TA GC column.
The results of the enantioselective Lewis acid cata-
lyzed cycloadditions of dienyl complexes 1a and 1b with
cyclohexenone are presented in Table 1. The mecha-
nism of the Lewis acid mediated demetallation shown
(
11–4) and the control reactions to prove that the
initially added achiral Lewis acid does not exchange
with subsequently added Lewis acids have been re-
ported previously [1h]. Corey’s monohalogenated boron
Lewis acid (6) [7] proved unreactive as a catalyst over
the temperature range of −45 to 25°C and dienyl
complex 1a was recovered in a \85% yield at all
temperatures (Table 1, entry 1). Since we had previ-
ously proven [1b,d,h] that diphenylglyoxime containing
dienyl complex 1b was less reactive than 1a, it was not
screened with Lewis acid 6. Isopinocampheyldichlorob-
orane (7) was an effective Lewis acid catalyst when used
with dienyl complex (1a) providing 4 with \20:1
diastereoselectivity for the anti (exo) product (Table 1,
entries 2–4). However, enantioselectivities were low at
temperatures where the reaction proceeded with a rea-
The Lewis acid catalysts screened (6–9 shown below)
are all readily available in high enantiomeric purity.

122
B.M. Richardson et al. / Journal of Organometallic Chemistry 577 (1999) 120–125
sonable rate. We have previously noted enhanced
stereoselectivities in cycloadditions using dienyl com-
plexes with larger equatorial ligands [1b,d,h], so
diphenylglyoxime dienyl complex (1b) was also exam-
ined with Lewis acid (7) (Table 1, entry 6). Enantiose-
lectivity improved (19% ee) but was still too low. We
have noted that rates of our Diels–Alder cycloaddition
slow substantially as the bulk of ligands and achiral
catalysts increase [1b,d,h], but we decided to look at
Hawkins bulky napthylcyclohexyl catalyst (8b) since it
was also a boron dihalide and had proven an effective
enantioselective Diels–Alder catalyst [11]. This catalyst
increase in enantioselectivity of up to 62% ee however,
the isolated yield of this enantiomerically enriched oc-
talone (4) was not as high as we had hoped for and this
reaction was complicated by the isolation of the trans
ring junction isomer in addition to 4. Further increases
in equatorial ligand size i.e the use of AliBu instead of
3
AlEt shut the cycloaddition down (Table 1, entry 13)
3
and use of the even bulkier binapthyl catalyst (9) also
shut down the cycloaddition and we recovered 1b in
high mass balance (Table 1, entry 14). All the successful
cycloadditions listed in Table 1 are also noteworthy in
that the cobaloxime complex (12a, b) was recovered in
a reusable form.
(
(
8b) proved unreactive when used with 1a at −45°C
Table 1, entry 7) but would effect cycloadditions (10%
ee) at −20°C (Table 1, entries 8 and 9). Switching to
the diphenylglyoxime diene (1b) (Table 1, entry 11)
required an increase in reaction temperature of up to
3. Conclusions
2
5°C to effect cycloaddition in 36 h. Enantioselectivity
In conclusion, we have demonstrated for the first
time that it is possible to effect Diels–Alder reactions
of cobaloxime containing dienyl complexes (1a and b)
with high exo (anti ) diastereoselectivities and reason-
able (up to 62% ee) enantioselectivities. We have
reached the upper limit of steric bulk which can be
tolerated in these cobaloxime dienyl complex cycloaddi-
tions so our future efforts on exo and enantioselective
Diels–Alder reactions will focus on Cosalen dienyl
complexes [1g].
improved substantially to 31% ee. Further increases in
reaction temperature were not possible due to the insta-
bility of dienyl complex (1b) toward Lewis acids at
elevated temperatures [1b,d,h]. Instead, we tried using
AlEt instead of AlMe in the initial Lewis acid for
Bronsted acid exchange reaction (Table 1, entry 12).
This change had increased equatorial ligand set bulk
and enhanced diastereoselectivities in our earlier achiral
Lewis acid studies [1d]. We did see a further large
3
3
Table 1
Cycloaddition reaction results
Entry
Diene
Catalyst
Time (h)
Temperature (°C)
Demetallationa
Yield 4
%ee
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1b
1b
1a
1a
1a
1b
1b
1b
1b
1b
6
7
7
7
7
7
8
8
8
8
8
8
8
9
6–24
3.5
3.5/2
16
10
5
24
24
36
24
−45 to 25
−45
−45/20
−20
−45
−20
−45
−20
−20/25
0
N/Ab
Two steps
In situ
No rxn (%)
64
72
67
No rxn
58
No rxn
84
N/Ab
7
7
1
c
Two steps
d
d
N/A
N/A
Two steps
N/A
Two steps
In situ
N/A
19
N/A
10
6
N/A
31
51
10
11
12
13
14
No rxn
65
36
36
36
6–24
25
25
25
In situ
In situ
e
27
62
N/A
N/A
f
f
N/A
No rxn
No rxn
g
g
−45 to 25
N/A
a
Two steps means 3 was isolated then treated with excess AlMe to demetallate to 4. In situ means 3 was not isolated, instead the cycloaddition
3
flask was allowed to warm to 25°C after the specified cycloaddition time to effect demetallation.
b
This catalyst was used at four different temperatures: −45°C/16 h; −20°C/24 h; 0°C/24 h; 25°C/6 h and in each case dienyl complex 1a was
recovered unreacted in \85% mass balance.
c
Reaction at −45°C for 3.5 h then warmed to 20°C for 2 h.
A \95% recovery of the diene (1b).
d
e
AlEt was used as the initial Lewis acid instead of AlMe . These conditions also lead to the production of the trans ring junction diastereomer
3
3
of 4 in a 44% yield.
f
AliBu3 was used as the initial Lewis acid instead of AlMe3 leading to a \85% recovery of the diene (1b).
This catalyst was used at four different temperatures: −45°C/16 h; −20°C/24 h; 0°C/24 h; 25°C/6 h and in each case dienyl complex 1b was
g
recovered unreacted in a \85% mass balance.

B.M. Richardson et al. / Journal of Organometallic Chemistry 577 (1999) 120–125
123
4. Experimental section
(R=Me) was then dissolved in dry THF (5 ml) and
cooled to 0°C, and AlMe (120 ml of a 2.0 M solution
3
in hexane, 0.240 mmol) was added via syringe. After 0.5
h, the solution was warmed to 25°C and allowed to stir
for 2.0 h. Water (2.0 ml) was added and the solution
was stirred for 10 min, CH Cl (25 ml) was added. The
4
.1. General methods
For a description of instrumentation and chromato-
2
2
graphic adsorbents used see Ref. [1b]. Cobalt chloride
hexahydrate used in the preparation of dienyl com-
plexes was purchased from Strem Chemicals and used
as received. Trimethylaluminum, triethylaluminum, tri-
isobutylaluminum and 2-cyclohexen-1-one were pur-
chased from Aldrich Chemicals and used as received.
The compounds (3E)-1,3-pentadien-2-yl-(pyridine)bis-
solution was then dried over MgSO . The Mg salts were
4
removed by vacuum filtration and washed with CH Cl
2
2
(
10 ml). The solvent was removed by rotary evapora-
tion and the resulting orange oil was chromatographed
on silica using 1:1 Et O/hexane to give 4 as a pale
2
yellow oil after solvent removal (19.9 mg, 0.136 mmol,
6
4%). This yellow oil was identical by spectroscopic
(
1
dimethylglyoximato) cobalt(III) (1a) [1b,e], and (3E)-
,3 - pentadien - 2 - yl - (pyridine)bis(diphenylglyoximato)
comparison to 4 reported previously [1h]. Resolution
of the enantiomers of 4 was carried out using the
method described in the general methods section
above. Further silica elution with EtOAc, followed by
removal of solvent with rotary evaporation and high
vacuum gave an orange solid, 12a, (64.5 mg, 0.168
mmol, 73%) identical by spectroscopic comparison to
cobalt(III) (1b) [1b,e], were prepared according to pre-
viously described methods. Enantioselectivities were de-
termined using an HP 5890 Series II Gas
Chromatograph with a Flame Ionization Detector. The
GC column used was a Chiraldex G-TA 0.25 mm×30
m trifluoroacetyl derivatized k cyclodextrin column pur-
chased from Advanced Separation Technologies, Incor-
porated (ASTEC). GC Method: injector temperature:
pyr(DMG) CoMe reported and characterized previ-
2
ously [1b,d,h, 15].
−
1
200°C; flow: 0.6 ml min ; split ratio: 75; oven pro-
gram: initial temperature was 120°C for 2 min then
4
2
.3. Diels–Alder reaction of diene (1a) and
-cyclohexen-1-one (2) catalyzed by isopinocampheyl
−
1
ramp 7°C min
up to a final temp of 160°C. This
method provided baseline resolution of the enantiomers
of an authentic racemic sample of 4 [1h]; retention
times of 10.018 and 10.355 min.
boron dichloride Lewis acid (7) (in situ clea6age)
The diene complex (1a) (100 mg, 0.23 mmol) was
dissolved in CH Cl (3.2 ml) and cooled to −45°C,
2
2
4
2
.2. Diels–Alder reaction of diene (1a) and
-cyclohexen-1-one (2) catalyzed by isopinocampheyl
and AlMe (230 ml of a 2.0 M solution in hexane, 0.46
3
mmol), which had been cooled to 0°C, was added and
gas evolution as well as a color change from light to
dark orange was noted. A standard stock solution of
boron dichloride Lewis acid (7) (two step demetallation
preparation)
2
-cyclohexen-1-one (1.0 ml of a 0.254 M solution in
Diene complex (1a) (100 mg, 0.23 mmol) was dis-
solved in CH Cl (3.2 ml) and cooled to −45°C. The
CH Cl , 0.254 mmol) which had been cooled to 0°C,
was then added quickly. Isopinocampheyl boron
2
2
2
2
compound AlMe3 (230 ml of a 2.0 M solution in
hexane, 0.46 mmol), which had been cooled to 0°C, was
added and gas evolution as well as a color change from
light to dark orange was noted. A standard stock
solution of 2-cyclohexen-1-one (1.0 ml of a 0.254 M
solution in CH Cl , 0.254 mmol) which had been
dichloride (7) (115 ml of a 1.0 M solution in CH Cl ,
2
2
0.115 mmol) was added and allowed to stir under N
2
for 3.5 h at −45°C. The reaction was then warmed to
20°C and allowed to stir for another 2 h. Water (1.5 ml)
was then added followed by CH Cl2 (10 ml). The
2
solution was dried with MgSO , vacuum filtered and
2
2
4
cooled to 0°C, was then added quickly. Isopinocam-
pheyl boron dichloride (7) (115 ml of a 1.0 M solution
in CH Cl ; 0.115 mmol) was then added and allowed to
the salts were washed with CH Cl (25 ml). The solvent
was removed by rotary evaporation and the resulting
orange oil was chromatographed on silica using 1:1
2
2
2
2
stir under N for 6 h. Water (1.5 ml) was then added
Et O/hexane to give 4 as a pale yellow oil after solvent
2
2
and the mixture was allowed to warm to 25°C, and
CH Cl (10 ml) was added. The solution was dried with
removal (27.3 mg, 0.167 mmol, 72%). This yellow oil
was identical by spectroscopic comparison to 4 reported
above. The mixture of enantiomers of 4 was resolved
using the method described above. Further elution with
EtOAc, followed by removal of solvent with rotary
evaporation and high vacuum gave an orange solid,
12a, (43.9 mg, 0.114 mmol, 49%) identical by spectro-
2
2
MgSO , vacuum filtered, and the salts were washed
4
with CH Cl (25 ml). The cycloadduct product was
2
2
purified on silica gel (ethyl acetate). The solvent was
removed by rotary evaporation and the resultant or-
ange powder was vacuum dried to give 3 (R=Me) (107
1
mg, 0.213 mmol, 93%) identical by H-NMR compari-
scopic comparison to pyr(DMG) CoMe reported and
2
son to previously reported material [1h]. Complex (3)
characterized previously [1b,d,h, 15].

124
B.M. Richardson et al. / Journal of Organometallic Chemistry 577 (1999) 120–125
4
2
.4. Diels–Alder reaction of diene (1b) and
-cyclohexen-1-one (2) catalyzed by isopinocampheyl
hexen-1-one (1.0 ml of a 0.254 M solution in CH Cl ,
2 2
0.254 mmol) which had been cooled to 0°C, was then
added quickly. The Lewis acid (8b) (230 ml of a 0.5 M
solution in CH Cl , 0.115 mmol) was added and allowed
boron dichloride Lewis acid (7)
2
2
The diene complex (1b) (200 mg, 0.30 mmol) was
dissolved in CH Cl (5 ml) and cooled to −20°C, and
to stir under N for 24 h. Water (1.5 ml) was subse-
2
quently added and the mixture was allowed to warm to
25°C before CH Cl (10 ml) was added. The solution was
2
2
AlMe (300 ml of a 2.0 M solution in hexane, 0.60 mmol),
3
2
2
which had been cooled to 0°C, was added and gas
evolution as well as a color change from light to dark
orange was noted. A standard stock solution of 2-cyclo-
hexen-1-one (1.30 ml of a 0.254 M solution in CH Cl ,
dried with MgSO , vacuum filtered and the salts were
4
washed with CH Cl (25 ml). The cycloadduct product
2
2
was purified on silica gel (ethyl acetate). The solvent was
removed by rotary evaporation and the resultant orange
solid was vacuum dried to give 3 (R=Me) (156.6 mg,
2
2
0
.33 mmol) which had been cooled to 0°C, was added
quickly. Isopinocampheyl boron dichloride Lewis acid
7) (150 ml of a 1.0 M solution in CH Cl , 0.150 mmol)
1
0.205 mmol, 89%) identical by H-NMR comparison to
(
material reported previously [1h]. Complex (3) (R=Me)
was then demetallated using the same second step proce-
dure described above for Lewis acid (7) and 1a. The
resulting orange oil was chromatographed on silica using
2
2
was added and the solution was allowed to stir under N2
for 5 h. Isopropanol/water (1:1, 1.5 ml) was then added
and the mixture was allowed to warm to 25°C at which
point CH Cl (10 ml) was added. The solution was dried
1:1 Et O/hexane to give 4 as a pale yellow oil after
2
2
2
with MgSO and then vacuum filtered and the salts were
solvent removal (28.3 mg, 0.173 mmol, 84%). This
yellow oil was identical by spectroscopic comparison to
4 reported above. Resolution of the enantiomers of 4
was carried out using the method described above.
Further elution with EtOAc, followed by removal of
solvent with rotary evaporation and high vacuum gave
an orange solid, 12a, (64.5 mg, 0.167 mmol, 55%)
4
washed with CH Cl (25 ml). The cycloadduct product
2
2
was purified on silica gel (CH Cl ). The solvent was
2
2
removed by rotary evaporation and the resultant orange
powder was vacuum dried to give 3 (R=Ph) (184 mg,
1
0
.241 mmol, 80%) identical by H-NMR comparison to
material reported previously [1h]. The cycloadduct was
dissolved in dry THF (5 ml) and cooled to 0°C and
identical
by
spectroscopic
comparison
to
AlMe (180 ml of a 2.0 M solution in hexane, 0.36 mmol)
pyr(DMG) CoMe reported and characterized previously
[1b,d,h, 15].
3
2
was added via syringe. After 0.5 h, the solution was
warmed to 25°C and allowed to stir for 2.0 h. Water (2.0
ml) was added and stirred for 10 min, CH Cl (25 ml)
4.6. Diels–Alder reaction of diene (1a) and
2-cyclohexen-1-one (2) catalyzed by Lewis acid (8b) (in
situ clea6age)
2
2
was added and the solution was dried over MgSO . The
4
Mg salts were removed by vacuum filtration and washed
with CH Cl (10 ml). The solvent was removed by rotary
2
2
evaporation and the resulting orange oil was chro-
The diene complex (1a) (100 mg, 0.23 mmol) was
dissolved in CH Cl (3.2 ml) and cooled to −20°C,
matographed on silica using 1:1 Et O/hexane to give 4
2
2
2
as a pale yellow oil after solvent removal (23.0 mg, 0.140
mmol, 58%) This yellow oil was identical by spectro-
scopic comparison to 4 reported above. Resolution of
the enantiomers of 4 was carried out using the method
described above. Further elution with EtOAc, followed
by removal of the solvent with rotary evaporation and
high vacuum gave an orange solid (12b), (99.6 mg, 0.162
mmol, 67%) identical by spectroscopic comparison to
AlMe (230 ml of a 2.0 M solution in hexane, 0.46 mmol),
3
which had been cooled to 0°C, was added and gas
evolution as well as a color change from light to dark
orange was noted. A standard stock solution of 2-cyclo-
hexen-1-one (1.0 ml of a 0.254 M solution in CH Cl ,
2
2
0.254 mmol) which had been cooled to 0°C, was then
added quickly. The Lewis acid (8b) (230 ml of a 0.5 M
solution in CH Cl , 0.115 mmol) was then added and
2
2
pyr(DPG) CoMe reported and characterized previously
allowed to stir under N for 36 h at −20°C. The reaction
2
2
[1b,d,h].
was then warmed to 20°C and allowed to stir for another
2
h. Water (1.5 ml) was added followed by CH Cl (10
2 2
4
2
.5. Diels–Alder reaction of diene (1a) and
-cyclohexen-1-one (2) catalyzed by Lewis acid (8b)
ml). The solution was dried with MgSO , vacuum
4
filtered and the salts were washed with CH Cl (25 ml).
2
2
(two step clea6age)
The solvent was removed by rotary evaporation and the
resulting orange oil was chromatographed on silica using
The diene complex (1a) (100 mg, 0.23 mmol) was
1:1 Et O/hexane to give 4 as a pale yellow oil after
2
dissolved in CH Cl (3.2 ml) and cooled to −20°C, and
solvent removal (19.2 mg, 0.117 mmol, 51%) This yellow
oil was identical by spectroscopic comparison to 4
reported above. The mixture of enantiomers of 4 was
resolved using the method described above. Further
elution with EtOAc, followed by removal of the solvent
2
2
AlMe (230 ml of a 2.0 M solution in hexane, 0.46 mmol),
3
which had been cooled to 0°, was added and gas
evolution as well as a color change from light to dark
orange was noted. A standard stock solution of 2-cyclo-

B.M. Richardson et al. / Journal of Organometallic Chemistry 577 (1999) 120–125
125
with rotary evaporation and high vacuum gave an orange
solid, 12a, (49.4 mg, 0.129 mmol, 56%) identical by
9007366). The Nebraska Center for Mass Spectrometry
(NSF DIR9017262) performed high resolution mass
spectral analyses. We thank Stefan Loren for helpful
discussions on the preparation of 8b.
spectroscopic comparison to pyr(DMG) CoMe reported
2
and characterized previously [1b,d,h, 15].
4
2
.7. Diels–Alder reaction of diene (1b) and
-cyclohexen-1-one (2) catalyzed by Lewis acid (8b)
References
(
in situ clea6age)
[
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T.L. Smalley, M.E. Welker, A.L. Rheingold, J. Am. Chem. Soc.
116 (1994) 6777. (c) H.L. Stokes, B.M. Richardson, M.W. Wright,
S.P. Vaughn, M.E. Welker, L. Liable-Sands, A.L. Rheingold,
Organometallics 14 (1995) 5520. (d) M.W. Wright, M.E. Welker,
J. Org. Chem. 61 (1996) 133. (e) H.L. Stokes, M.E. Welker,
Organometallics 15 (1996) 2624. (f) M.W. Wright, H.L. Stokes,
B.M. Richardson, T.A. Adams, T.L. Smalley, S.P. Vaughn, G.J.
Lohr, M.E. Welker, L. Liable-Sands, A.L. Rheingold, Advances
in Cycloaddition 4 (1997)149 ; M. Lautens (Ed.), JAI Press,
Greenwich, Conn. (g) J.J. Chapman, M.E. Welker, Organometal-
lics 16 (1997) 747. (h) B.M. Richardson, M.E. Welker, J. Org.
Chem. 62 (1997) 1299. (i) T.A. Adams, M.E. Welker, L. Liable-
Sands, A.L. Rheingold, Organometallics 16 (1997) 1300. (j) T.A.
Adams, M.E. Welker, C.S. Day, J. Org. Chem. 63 (1998) 3683.
2] (a) M. Tada, T. Shimizu, Bull. Chem. Soc. Jpn. 65 (1992) 1252.
The diene complex (1b) (150 mg, 0.225 mmol) was
dissolved in CH Cl (4 ml) and cooled to −20°C, AlMe
2
2
3
(
225 ml of a 2.0 M solution in hexane, 0.450 mmol), which
had been cooled to 0°C, was added and gas evolution as
well as a color change from light to dark orange was
noted. A standard stock solution of 2-cyclohexen-1-one
(
1.0 ml of a 0.254 M solution in CH Cl , 0.254 mmol)
2 2
which had been cooled to 0°C, was then added quickly.
The Lewis acid (8b) (230 ml of a 0.5 M solution in CH Cl ,
0
2
ml) was added followed by CH Cl (10 ml). The solution
was dried with Na SO , vacuum filtered and the salts
were washed with CH Cl (25 ml). The solvent was
removed by rotary evaporation and the resulting orange
oil was chromatographed on silica using 1:1 Et O/hexane
2
2
.115 mmol) was added and the solution was warmed to
5°C and allowed to stir under N for 36 h. Water (1.5
2
2
2
[
[
2
4
(
b) M. Tada, N. Mutoh, T. Shimizu, J. Org. Chem. 60 (1995) 550.
2
2
3] For a recent reviews of transition-metal mediated cycloaddition
reactions see: (a) H.-W. Fruhauf, Chem. Rev. 97 (1997) 523. (b)
M. Lautens, W. Klute, W. Tam, Chem. Rev. 96 (1996) 49.
2
to give 4 as a pale yellow oil with other byproducts. This
product was then chromatographed on a silica prep plate
using 1:4 Et O:pentane (R =0.58) to give a pale yellow
oil (21.3 mg, 0.130 mmol, 58%). This yellow oil was
identical by spectroscopic comparison to 4 reported
above. The mixture of enantiomers of 4 was resolved
using the method described above. The organometallic
product from the cleavage reaction is eluted from the
[4] (a) T.S. Powers, W. Jiang, J. Su, W.D. Wulff, B.E. Waltermire,
A.L. Rheingold, J. Am. Chem. Soc. 119 (1997) 6438 and references
therein. (b) J. Barluenga, R.-M. Canteli, J. Florez, S. Garcia-
Granda, A. Gutierrez-Rodriguez, E. Martin, J. Am. Chem. Soc.
2
f
1
20 (1998) 2514 and references therein. (c) M. Sabat, K.A.
Reynolds, M.G. Finn, Organometallics 13 (1994) 2084. (d) S.R.
Gilbertson, X. Zhao, D.P. Dawson, K.L. Marshall, J. Am. Chem.
Soc. 115 (1993) 8517.
[
5] For a recent reviews of thermal and Lewis acid catalyzed Diels–
Alder reactions of 2-cyclohexenones see: (a) F. Fringuelli, L.
Minuti, F. Pizzo, A. Taticchi, Acta Chem. Scand. 47 (1993) 255.
original silica column with 1:1 Et O:pentane. The solvent
2
was removed by rotary evaporation and the orange
powder was vacuum dried to give 12b, (115 mg, 0.182
mmol, 81%) identical by spectroscopic comparison to
(
b) F. Fringuelli, A. Taticchi, E. Wenkert, Org. Prep. Proc. Int.
22 (1990) 131.
[
[
6] For reviews of asymmetric catalysts used in Diels–Alder reactions
see: (a) T. Oh, M. Reilly, Org. Prep. Proc. Int. 26 (1994) 129. (b)
L. Deloux, M. Srebnik, Chem. Rev. 93 (1993) 763. (c) H.B. Kagan,
O. Riant, Chem. Rev. 92 (1992) 1007.
7] (a) E.J. Corey, R. Imwinkelried, S. Pikul, Y.B. Xiang, J. Am.
Chem. Soc. 111 (1989) 5493. (b) E.J. Corey, S. Sarshar, D.-H. Lee,
J. Am. Chem. Soc. 116 (1994) 12089.
pyr(DPG) CoMe reported and characterized previously
2
[1b,d,h].
5. Supplementary material
[
[
8] S. Pikul, E.J. Corey, Org. Synth. 71 (1992) 22.
9] (a) R. Soundararajan, D.S. Matteson, J. Org. Chem. 55 (1990)
Details of the crystallographic characterization of 8a
are available from C.S. Day at the following e-mail
address (daycs@wfu.edu).
2
274. (b) R. Soundararajan, D.S. Matteson, Organometallics 14
1995) 4157.
[10] H.C. Brown, V.K. Mahindroo, U.P. Dhokte, J. Org. Chem. 61
1996) 1906.
11] (a) J.M. Hawkins, S.J. Loren, J. Am. Chem. Soc. 113 (1991) 7794.
(
(
[
(
(
b) J.M. Hawkins, S. Loren, M. Nambu, J. Am. Chem. Soc. 116
1994) 1657.
Acknowledgements
[
12] (a) K. Mikami, M. Terada, T. Nakai, J. Am. Chem. Soc. 111
(1989) 1940. (b) K. Mikami, M. Terada, Y. Motoyama, T. Nakai,
Tetrahedron Asymmetry 2 (1991) 643.
We thank the National Science Foundation (CHE-
9
321454 and CHE-9726172), and the Camille and Henry
[
[
13] M.T. Reetz, S.-H. Kyung, C. Bolm, T. Zierke, Chem. Ind. (1986)
Dreyfus Foundation (Henry Dreyfus Teacher-Scholar
Award to M.E.W, 1994–99) for their support. Low
resolution mass spectra were obtained on an instrument
purchased with the partial support of NSF (CHE-
8
24.
14] Details of the crystallographic characterization of 8a are available
from C.S. Day at the following e-mail address (daycs@wfu.edu).
[15] G.N. Schrauzer, Inorg. Synth. 11 (1968) 61.